heart failure , comorbidities , niddm , sglt2, coronary artery disease, chronic kidney disease, iron deficiency

1. Managing comorbidities in Heart Failure
DR ASHWANI MEHTA
Senior Consultant Cardiologist
Sir Ganga Ram Hospital
New Delhi

2. 1. Mozaffarian D et al. Circulation. 2015;131(4):e29-e322.
2. Mosterd A et al. Heart. 2007;93(9):1137-1146.
3. http://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/Chronic-Conditions/Downloads/2012Chartbook.pdf
4. Cowie MR et al. Oxford PharmaGenesis; 2014. http://www.oxfordhealthpolicyforum.org/AHFreport. Accessed February 18, 2015.
5. Fauci AS et al. Harrison's Principles of Internal Medicine. 17th ed. New York: McGraw-Hill; 2008.
6. Cook C et al. Int J Cardiol. 2014;171(3):368-376.
NUMBER of PATIENTS
21 MILLION adults worldwide are
living with heart failure
This number is expected to
rise.1,2
The Burden of Heart failure
REHOSPITALISATION
Heart failure is the NUMBER 1
cause of hospitalisation for
patients aged >65 years.4
MORTALITY
50% of heart failure patients die
within 5 years from diagnosis.5
COMORBIDITIES: The vast
majority of HF patients has 3 or
more comorbidities 3
ECONOMIC BURDEN
In 2012, the overall worldwide
cost of heart failure was nearly
$108 BILLION.6

3. Comorbidities impact prognosis in patients with HF1,2
1. McMurray et al. Eur Heart J 2012;33:1787–847
2. Ennezat et al. Nephrol Dial Transplant 2011;26:3908-13
Why comorbidities are relevant in HF1:
• Associated with worse clinical status and
are predictors of poor prognosis .
• Drugs -worsening of HF
• Drugs -may interact and reduce patient
adherence
COPD
Gout
Hyperlipidaemia
Iron deficiency
Renal
dysfunction
Diabetes mellitus
Anaemia
Cachexia
Obesity
Comorbidities in
patients with HF
Hypertension
Angina
Depression
Sleep disturbance
Cancer
Co-morbidities in HFCo-morbidities in HF

4. J Am Coll Cardiol. 2018 Jan 16;71(2):201-230

5. Ten Principles for Successful Treatment of Heart Failure

6. Common Cardiac Comorbidities With HFrEF
J Am Coll Cardiol. 2018 Jan 16;71(2):201-230

7. Noncardiac Comorbidities With HFrEF
J Am Coll Cardiol. 2018 Jan 16;71(2):201-230

9. Dealing with comorbidities in heart failure
Iron deficiency:
A comorbidity that goes
unnoticed in heart failure
Iron deficiency is an important comorbidity and is
prevalent in patients with heart failure ;
however, it is often neglected.

10. Iron Deficiency is common in patients with HF
8-10 Mn Individuals
are affected by Heart
Failure in India 1
1 - Chaturvedi et al Heart failure in India. The Indus Study
6-8 Mn Iron Deficiency
in CHF patients in India 2
3 out of 4
Heart failure
patients have
ID in India
Country wise ID prevalence in HF
USA
61.3%
Europe
37-50 %
Singapore
61.4 %
Singapore Indian
82 %
S.K. Sharma et.al. Indian Heart J. 2016 Jul-Aug; 68(4): 493–497.
Alarming burden of ID with HF in India
Up to 50% of patient with HF have concomitant Iron Deficiency

11. 2016 ESC HF guidelines
Iron deficiency in Heart Failure
Iron deficiency in patients with HF:
a common and important comorbidity
irrespective of the presence of anaemia
Decreased exercise performance
Impaired health-related quality of life
Worse prognosis

12. All patients with HF are recommended to be screened for
iron deficiency based on serum ferritin and TSAT

13. ESC 2016 HF guidelines recommend considering intravenous
ferric carboxymaltose to treat iron deficiency in HFrEF
FCM, ferric carboxymaltose; HF, heart failure; HFrEF, HF with reduced ejection fraction
Ponikowski P et al. Eur Heart J. 2016;37:2129-200
Recommendations Class Level
Iron deficiency
Intravenous ferric carboxymaltose FCM
should be considered in symptomatic
patients with HFrEF and iron deficiency
(serum ferritin <100 µg/L, or ferritin
between 100-299 µg/L and transferrin
saturation <20%) in order to alleviate
HF symptoms, and improve exercise
capacity and quality of life.
IIa A
Recommendation
based on:
FAIR-HF &
CONFIRM-HF
Studies published after
2016 HF guidelines
EFFECT-HF (with FCM)
IRON-OUT (oral iron)

14. Recurrent event outcomes
FCM
(N=504)
Placebo (N=335) Rate Ratio (95%CI) p
CV hospitalization and CV death 69 (23.0) 92 (40.9) 0.59 (0.40-0.88) 0.009
HF hospitalization and CV death 39 (13.0) 60 (26.7) 0.53 (0.33-0.86) 0.011
CV hospitalization and all-cause death 71 (23.7) 94 (41.8) 0.60 (0.41-0.88) 0.009
HF hospitalization and all-cause death 41 (13.7) 62 (27.6) 0.54 (0.34-0.87) 0.011
All-cause hospitalization and all-cause
death
108 (36.1) 118 (52.5) 0.73 (0.52-1.01) 0.060
HF hospitalization 22 (7.3) 43 (19.1) 0.41 (0.23-0.73) 0.003
CV hospitalization 52 (17.4) 75 (33.3) 0.54 (0.36-0.83) 0.004
All-cause hospitalization 89 (29.7) 99 (44.0) 0.71 (0.50-1.01) 0.056
Meta-analysis on individual patient data with FCM
Efficacy outcomes based on 839 patients
Rate ratio analysis (recurrent event analyses)
Anker SD, et al. Eur J Heart Fail 2017

15. Algorithm for the diagnosis and treatment/follow-up
of iron deficiency in CHF patients
McDonagh T et al. Eur J Heart Fail 2018;20:1664-72
Chronic HFrEF
(NYHA II-IV)
Ferritin
100–299 μg/L,
when TSAT <20%
Check iron deficiency status
Ferritin
<100 μg/L OR
YES
Step
1
Step
2
Check anaemia status
Male Hb <13 g/dL Female Hb <12 g/dL
NO YES
Step
3
Exclude other causes for
anaemia depending
on clinical status
Iron deficiency treatment
If Hb >15 g/dL, do not administer IV iron
No other cause
Consider ferric carboxymaltose as
500−1000 mg single doses of iron to correct iron deficiency
Dosing calculations according to haemoglobin levels and body weight
Haemoglobin Patient body weight
g/dL mmol/L <35 kg 35 kg − <70 kg ≥70 kg
<10 <6.2 500 mg 1500 mg 2000 mg
10−14 6.2–8.7 500 mg 1000 mg 1500 mg
>14 >8.7 500 mg 500 mg 500 mg
Check ferritin + TSAT
at next scheduled visit (preferable at 3 months)
Step
4
Check ferritin + TSAT
1−2 times per year or if change in clinical picture
or if haemoglobin decreases
Step
5

16. •Heart failure (HF) interacts with kidney disease via numerous pathophysiological
pathways in both the acute and chronic setting1
•Mounting data indicate that the complex interplay between the heart and the kidneys
involves haemodynamic, (neuro)homonal and cardiovascular disease-associated
mechanisms1
•Acceleration of HF or kidney dysfunction is driven by impairment of either the heart
or kidneys via mechanisms including induction of inflammation, activation of the
cellular immune system, metabolic disorders, anaemia and mineral and bone disorder1
1. Nature Reviews Nephrology volume 12, pages 610–623 (2016)
2. N Shiba et al. Journal of Cardiology (2011) 57, 8—17
Heart Failure & Kidney Disease

17. All-cause mortality’in patients with HF CVD-specific mortality’ in patients with HF
34 460 patients diagnosed with HF from 2003 to 2016
All-cause and CVD-specific mortality risks increased with increasing
multimorbidity
Kaur P, et al. BMJ Open 2018;8:e021291.
HF + CKD : The consequence when they co-exist

18. • CKD is now pandemic and affects more than 16% of adult population.
• CKD is a common co-morbidity in patients with Heart Failure.
• The co-existence of HF and CKD will increase the toxic manifestation of
various diagnostic and therapeutic measures, accelerates atherosclerosis
and increases the risk of death
• More than 40% of HF patients have CKD and the close relationship between
CKD and HF worsens their prognoses
Chronic Kidney disease

19. ARNI Vs Acei: Renal Safety
No significant difference in progression of renal dysfunction with LCZ696 , compared
with Enalapril
LCZ 696 slows the progression of renal dysfunction and improved clinical outcomes,
even in patients with CKD.
Desai AS.et al.JAMA Cardiol. 2017;2(1):79-85
LCZ696

20. Change in Estimated Glomerular Filtration Rate
Compared with enalapril, sacubitril/valsartan led to a slower rate of decrease in the
eGFR and improved cardiovascular outcomes, even in patients with chronic kidney
disease,

21. ARNI :Renal Safety : Hyperkalemia
The risk of hyperkalemia associated with the use of MRA’s was lower among those treated
with LCZ696 than those treated with Enalapril1
Use of LCZ696 in preference to ACEI may enhance the ability to use MRA’s
safely, allowing patients to reap the incremental benefits at less additional risk.
Desai AS.et al.JAMA Cardiol. 2017;2(1):79-85

22. Spannella F et al. Internal and Emergency Medicine (2019) 14:1287–
1297
Changes e-GFR Changes in serum potassium

23. Diabetes and heart failure

24. Heart failure with Diabetes
• Mortality X 10 times
• 5-yr survival 12.5%
Khan SS, Butler J, Gheorghiade M. Management of comorbid diabetes mellitus and worsening heart failure.JAMA2014;311:2379-
80.
Heart
Failure
Recurrent
Hospitalization
Poor QOL
Higher
Mortality
50% of diabetics develop HF in lifetime

25. Bidirectional Impact of Diabetes and CHF
Campbell P, et al. Cardiac Failure Review. 2015;1(1):8.
FFA = free fatty acids: Ca2+ = Calcium; Renin-angiotensin aldosterone system;
LVH = Left ventricular hypertrophy.
Adapted from Campbell P, 2015
Altered FFA metabolism
Diabetes Mellitus
01
Impaired myocyte
Ca2+ sensitivity02
Microvascular
dysfunction03
Neurohormonal
abnormalities (RAAS)04
Cardiac autonomic
dysfunction05
Hyperglycaemic cellular
damage06
Altered myocyte
metabolism
Endothlieal
dysfunction
Myocyte necrosis
LVH
Fibrosis
Relaxation
abnormalities
Impaired LV
contractile function

26. SGLT2 Inhibitors: New Promising Agents In T2DM patients with HF
Tanaka A, et al. Cardiovascular Diabetology. 2016;15(1). SGLT-2, Sodium-glucose co-transporter 2; BP, blood pressure; BW, body weight, CV, cardiovascular; CHF, congestive heart failure, T2DM,
type2 diabetes mellitus
Novel Mechanisms
Fuel Shift
NHE mediated effects
Interstitial volume
Cardiac remodeling
Heme Oxygenase (HO-1)
Increased Hematocrit

27. ADA 2020 : SGLT2i is the preferred OHA in T2DM patients with
ASCVD , HF or CKD
First line therapy is Metformin and Comprehensive Lifestyle (Including Weight
Management and Physical Activity)

28. Empagliflozin should be considered in patients with
T2DM “in order to prevent or delay the onset of heart failure or prolong life

29. DAPA HF - A Game Changer
N Engl J Med. 2019 Sep 19.

30. DAPA HF - A Game Changer
N Engl J Med. 2019 Sep 19.
Among patients with heart failure and a reduced ejection fraction, the risk of
worsening heart failure or death from cardiovascular causes was lower among
those who received dapagliflozin than among those who received placebo,
regardless of the presence or absence of diabetes.

31. Abhinav Sharma et al. JCHF 2018;6:813-822
©2018 by American College of Cardiology

32. Summary
• Comorbidities are frequent and may be overlooked during routine CHF
management.
• They have great impact on hospitalisations and mortality.
• The most important comorbidities in heart failure patients are renal insufficiency,
diabetes mellitus, COPD, sleeping disorders like obstructive and central apnea
syndrome and anemia.
• Managing comorbidities is essential as it play an integral role in HF progression
and response to treatment.